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Biomedical subjects

S Hu

Publications and source records attributed to S Hu.

At least 217 records · Page 12Linked to original sources
PubMed1997

I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-induced apoptosis.

The pivotal discovery that the death proteases caspase 8 (FLICE) and caspase 10 (Mch4/FLICE2) are recruited to the CD-95 and tumor necrosis factor receptor-1 signaling complexes suggested a mechanism used by these cytotoxic receptors to initiate apoptosis. In this report, we describe the cloning and characterization of I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-induced apoptosis. The overall architecture of I-FLICE is strikingly similar to that of FLICE and Mch4/FLICE2. However, I-FLICE lacks both a catalytic active site and residues that form the substrate binding pocket, in keeping with its dominant negative inhibitory function. I-FLICE is the first example of a catalytically inert caspase that can inhibit apoptosis.

Adult↗
PubMed1997

Activation of BK(Ca) channel via endothelin ET(A) receptors in porcine coronary artery smooth muscle cells.

It has been demonstrated previously that endothelin-1 stimulates the Ca2+-activated K+ (BK(Ca)) channel activity in porcine coronary artery smooth muscle cells. The purpose of the present study was to delineate the endothelin receptor subtype involved in this action. In receptor binding studies, [125I]endothelin-1 was shown to bind to the homogenate of porcine primary coronary artery smooth muscle cells in a single class of binding sites with K(D) and Bmax values of 73 pM and 99 fmol/mg protein, respectively. Furthermore, endothelin-1 and endothelin-3 displaced the binding of [125I]endothelin-1 to these cells with respective IC50 values of 70 and 17000 pM, a 240-fold difference in potency. The effects of endothelin-3 on the activity of the BK(Ca) channel in porcine coronary artery smooth muscle cells were examined using the cell-attached patch-clamp technique. Similar to endothelin-1, endothelin-3 also exhibited a bell-shaped concentration-response curve. A maximal increase of 95% in channel open-state probability (Po) was induced by 100 nM endothelin-3 as compared with the 320% increase in Po by 1 nM endothelin-1. Thus, endothelin-1 was about 100-fold more potent and 3.4-fold more efficacious than endothelin-3 in this action. Both the receptor binding and the electrophysiological results suggest that the effects of endothelins on the BK(Ca) channel are mediated through the endothelin ET(A) receptor subtype.

Animals↗
PubMed1997

A novel family of viral death effector domain-containing molecules that inhibit both CD-95- and tumor necrosis factor receptor-1-induced apoptosis.

Molluscum contagiosum virus proteins MC159 and MC160 and the equine herpesvirus 2 protein E8 share substantial homology to the death effector domain present in the adaptor molecule Fas-associated death domain protein (FADD) and the initiating death protease FADD-like interleukin-1beta-converting enzyme (FLICE) (caspase-8). FADD and FLICE participate in generating the death signal from both tumor necrosis factor receptor-1 (TNFR-1) and the CD-95 receptor. The flow of death signals from TNFR-1 occurs through the adaptor molecule tumor necrosis factor receptor-associated death domain protein (TRADD) to FADD to FLICE, whereas for CD-95 the receptor directly communicates with FADD and then FLICE. MC159 and E8 inhibited both TNFR-1- and CD-95-induced apoptosis as well as killing mediated by overexpression of the downstream adaptors TRADD and FADD. Neither viral molecule, however, inhibited FLICE-induced killing, consistent with an inhibitory action upstream of the active death protease. These data suggest the existence of a novel strategy employed by viruses to attenuate host immune killing mechanisms. Given that bovine herpesvirus 4 protein E1.1 and Kaposi's sarcoma associated-herpesvirus protein K13 also possess significant homology to the viral inhibitory molecules MC159, MC160, and E8, it may be that this class of proteins is used ubiquitously by viruses to evade host defense.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Inhibition of swine microglial cell phagocytosis of Cryptococcus neoformans by femtomolar concentrations of morphine.

Microglia are important immune effector cells within the brain. The phagocytosis of nonopsonized Cryptococcus neoformans by swine microglia was used as an in vitro model for studies on cellular mechanisms of opiate-mediated immunomodulation in the brain. Morphine inhibited potently (IC50 approximately 10(-16) M) the phagocytosis of C. neoformans by primary cultures of neonatal pig microglia. The mu opioid agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) also suppressed phagocytosis but with a much lower potency than morphine (IC50 approximately 10(-8) M). The inhibitory effects of morphine and DAMGO were blocked by equimolar concentrations of naloxone and by the selective mu opiate receptor antagonist beta-funaltrexamine. Pertussis toxin but not cholera toxin reversed the inhibitory effects of both morphine and DAMGO. Our data suggest that morphine inhibits phagocytosis of C. neoformans by swine microglia via a mechanism involving mu opiate receptors coupled to a pertussis toxin-sensitive Gi/G(o) protein signaling pathway.

Animals↗
PubMed1997

Proinflammatory cytokines inhibit HIV-1(SF162) expression in acutely infected human brain cell cultures.

An understanding of how viral replication in glial cells responds to proinflammatory cytokines is important in delineating HIV-1 neuropathogenesis. Because no information is available in the literature regarding the regulatory effects of exogenous cytokines on acute HIV-1 replication in human brain cells, we studied the impact of cytokine treatment on viral p24 Ag expression. Based upon reports using mononuclear phagocytes derived from somatic sources, we hypothesized that TNF-alpha, IL-1 beta, and IL-6 would up-regulate the expression of HIV-1(SF162) (a monocytotropic strain) in purified microglial cells and in mixed brain cell cultures. This hypothesis was not supported. In fact, a contrary, unexpected result was obtained; whereas in purified microglial cultures TNF-alpha displayed a mild stimulatory effect on HIV-1 expression (15% increase in p24 Ag production compared with control cultures), surprisingly, IL-1 beta and IL-6 were highly suppressive (91 and 83% inhibition of HIV expression, respectively). In contrast to the findings in microglial cell cultures, TNF-alpha profoundly suppressed (84%) HIV-1 expression in mixed brain cell cultures, as did IL-1 beta (82%), and IL-6 was moderately suppressive (55% inhibition). In an attempt to identify factors responsible for the differential effects of TNF-alpha in the two brain cell infection models, it was found that compared with microglial cell cultures, TNF-alpha treatment of mixed brain cell cultures released significantly greater amounts of RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1 alpha, beta-chemokines that have been suggested to have anti-HIV-1 effects. Thus, these data suggest that proinflammatory cytokines possess anti-HIV-1 activity in the central nervous system.

Acute Disease↗
PubMed1997

Primary varicella-zoster keratitis: diagnosis by polymerase chain reaction.

PURPOSE: To report the value of polymerase chain reaction in the diagnosis of a worsening corneal ulcer. METHODS: A 6-year-old boy underwent an emergent penetrating keratoplasty for a corneal ulcer that continued to worsen despite intensive antibiotic therapy. RESULTS: Examination of the corneal specimen by polymerase chain reaction was positive for varicella-zoster virus but negative for herpes simplex. Based on polymerase chain reaction studies, we diagnosed primary varicella-zoster keratitis with corneal perforation. Electron microscopy showed herpetic virus particles in the cornea. CONCLUSIONS: Polymerase chain reaction analysis of corneal buttons at the time of penetrating keratoplasty may benefit patients with undiagnosed recalcitrant corneal ulcers.

Child, Preschool↗
PubMed1997

p53 expression and proliferative activity in Bowen's disease with or without chronic arsenic exposure.

A comparative study of Bowen's disease (BD) with or without chronic arsenic exposure may contribute to understanding arsenic carcinogenesis. We compared the p53 overexpression and proliferative activity of 26 cases of BD with chronic arsenic exposure (group I) and 22 comparable cases of BD without chronic arsenic exposure (group II) by immunohistochemical method on formalin-fixed, paraffin-embedded tissues with antibodies PAb1801 and MIB-1, respectively. We also included in this study two squamous cell carcinomas that developed from BD in group I and one in group II. Two paired BD lesions in the same individual of one patient in group I and of three patients in group II were also studied. The significant p53(+) (>10% stained cells) rates were 42.3% (11 of 26) and 9.1% (2 of 22) for groups I and II, respectively, and the difference was statistically significant (P = .01). The p53 expression in different lesions of the same individual remained consistently the same. Squamous cell carcinomas that developed in 2 cases of p53(+) BD in group I were also positive, but the one in 1 case of p53(-) BD in group II was negative. No significant statistical difference in proliferative activity was found between group I BD and group II BD (P= .769), nor between p53(+) cases (>10% stained cells) and p53(-) cases (<10% stained cells) in group I BD (P = .519). This study showed that significant overexpression of p53 protein was higher in BD with chronic arsenic exposure. Therefore, arsenic carcinogenesis of BD might be different from that of BD unrelated to arsenic, and alteration of p53 plays a more important role in the pathogenesis of BD with chronic arsenic exposure. Overexpression of p53 was not a prerequisite for developing squamous cell carcinoma and was not affected by proliferative activity.

Adult↗
PubMed1997

A pattern classification procedure integrating the multivariate statistical analysis with neural networks.

A new procedure integrating multivariate statistical analysis with artificial neural networks (ANN) for complex pattern classification is proposed. Firstly, a specially designed statistical analysis algorithm called correlative component analysis (CCA) was used to identify the classification characteristics (CC) from original high-dimensional pattern information. These CC were then used as input data to the ANN for pattern classification. The proposed new procedure not only effectively decreased the dimensionality of original patterns, but also took advantage of the self-learning power of the ANN. Further, a typical example of classifying natural spearmint essence was employed to verify the effectiveness of the new pattern classification method. The study showed that this novel integrated procedure provides better results than those obtained using individual methods separately.

Algorithms↗
PubMed1997

Elevation of bioactive transforming growth factor-beta in serum from patients with chronic fatigue syndrome.

The level of bioactive transforming growth factor-beta (TGF-beta) was measured in serum from patients with chronic fatigue syndrome (CFS), healthy control subjects, and patients with major depression, systemic lupus erythematosis (SLE), and multiple sclerosis (MS) of both the relapsing/remitting (R/R) and the chronic progressive (CP) types. Patients with CFS had significantly higher levels of bioactive TGF-beta levels compared to the healthy control major depression, SLE, R/R MS, and CP MS groups (P < 0.01). Additionally, no significant differences were found between the healthy control subjects and any of the disease comparison groups. The current finding that TGF-beta is significantly elevated among patients with CFS supports the findings of two previous studies examining smaller numbers of CFS patients. In conclusion, TGF-beta levels were significantly higher in CFS patients compared to patients with various diseases known to be associated with immunologic abnormalities and/or pathologic fatigue. These findings raise interesting questions about the possible role of TGF-beta in the pathogenesis of CFS.

Depression↗
PubMed1997

Potent inhibitory effect of tetrandrine on experimental allergic conjunctivitis in mice.

This study investigated the effectiveness of tetrandrine (TDR) on experimental allergic conjunctivitis secondary to ragweed pollen. SWR/J mice were divided as follows: group 1, normal controls; group 2, sensitized but untreated; group 3, sensitized, buffered saline (BS)-treated; and group 4, sensitized, TDR-treated. The last three groups were exposed to ragweed through topical contact on the nasal and conjunctival mucosae followed by challenge with the allergen on the conjunctiva. Groups 3 and 4 received doses of BS and TDR, respectively. The allergic conjunctivitis was evaluated by scoring of the clinical signs and histopathology. mRNA gene expression of interleukin 1 beta (IL-1 beta) and IL-5 in the conjunctiva was analyzed by polymerase chain reaction techniques. All mice exposed to ragweed developed allergic conjunctivitis clinically and histologically. The conjunctivitis was significantly modulated by intraperitoneal injection of a new anti-inflammatory agent, TDR. Histopathologic analysis demonstrated that TDR strikingly reduced the conjunctival eosinophil infiltration and the number of intact and degranulating mast cells. IL-1 beta and Il-5 mRNA gene expression in the conjunctiva of TDR-treated mice was dramatically down-regulated compared with untreated and BS-treated controls. The results indicate that TDR may have potential clinical use in the treatment of conjunctivitis.

Alkaloids↗
PubMed1997

Differential production of and migratory response to beta chemokines by human microglia and astrocytes.

Little is known about the participation of beta chemokines in inflammatory processes within the central nervous system. The release of three of these peptides (macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and monocyte chemoattractant protein-1) from human fetal microglial cell and astrocyte cultures was assessed following stimulation by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha. Although striking differences were found between these two types of glial cells in their responsiveness to lipopolysaccharide and cytokines, both microglia and astrocytes produced all three beta chemokines. Only microglial cells, however, demonstrated an increased migratory response to the beta chemokines. The results of this in vitro study suggest that beta chemokines may play an important role in the trafficking of mononuclear phagocytes within the brain.

Astrocytes↗
PubMed1997

Cutaneous involvement in polyvinylpyrrolidone storage disease: a clinicopathologic study of five patients, including two patients with severe anemia.

Polyvinylpyrrolidone (PVP), formerly a plasma expander, has continued to be inappropriately used in Taiwan for intravenous injection as a "blood tonic." Five cases of PVP storage disease with cutaneous involvement were studied. Two patients presented with cutaneous eruptions mimicking collagen vascular disease and chronic pigmented purpuric dermatosis. Two other cases were found incidentally: one was with a metastatic tumor and the other in a pemphigus lesion. The fifth case was seen in a blind skin biopsy specimen taken to exclude Niemann-Pick disease after hematologic examination of a bone marrow smear. The latter patient and the patient with a collagen vascularlike disease also had severe anemia and serious orthopedic and neurologic complications due to massive infiltration of PVP-containing cells in the bone marrow with destruction of the bone. Severe irreversible anemia due to PVP storage disease has not been reported before. Three patients admitted having a history of receiving intravenous injection of PVP. The samples obtained from two of them indeed contained 5% PVP as determined by chemical analysis. PVP storage disease can be diagnosed by its histopathologic features. The skin biopsy specimens all showed a variable number of characteristic blue-gray vacuolated cells around blood vessels and adnexal structures with positive tinctorial reactions to mucicarmine, colloidal iron, and alkaline Congo red and negative to periodic acid-Schiff (PAS) and alcian blue. The PVP storage cells were shown to be CD68+ macrophages. The presence of PVP in the skin induced little or no inflammatory reaction. Only the pelvic mass in one patient had a foreign body granuloma formation. Our study showed that systemic parenteral administration of PVP preparation could result in the accumulation of PVP storage cells in the skin, with or without clinical eruptions. The diagnosis of systemic PVP storage disease can be established by performing a skin biopsy for pathologic study. It is important for pathologists and clinicians to be aware of this iatrogenic storage disease to avoid misdiagnosis for hereditary storage disease, osteomyelitis, or signet-ring cell carcinoma. Serious hematologic and orthopedic complications can be caused by repeated massive intravenous injection of PVP. Therefore, PVP preparations should be strictly prohibited for systemic administration.

Adult↗
PubMed1997

Diazepam-mediated inhibition of human immunodeficiency virus type 1 expression in human brain cells.

Treatment of acutely infected human brain cell and enriched microglial cell cultures with diazepam inhibited human immunodeficiency virus type 1 (HIV-1) p24 antigen expression. Similarly, diazepam suppressed HIV-1 expression in chronically infected promonocytic (U1) cells and acutely infected monocyte-derived macrophages, and this antiviral activity was associated with decreased activation of nuclear factor kappa B.

Anti-Anxiety Agents↗
PubMed1997

Intrauterine growth retardation in Iowa communities with herbicide-contaminated drinking water supplies.

In a statewide survey of 856 Iowa municipal drinking water supplies in 1986-1987 the Rathbun rural water system was found to contain elevated levels of triazine herbicides. Rates of low birth weight, prematurity, and intrauterine growth retardation (IUGR) in live singleton births during the period 1984-1990 by women living in 13 communities served by the Rathbun water system were compared to other communities of similar size in the same Iowa counties. The Rathbun communities had a greater risk of IUGR than southern Iowa communities with other surface sources of drinking water (relative risk = 1.8; 95% CI = 1.3, 2.7). Multiple linear regression analyses revealed that levels of the herbicides atrazine, metolachlor, and cyanzinc were each significant predictors of community IUGR rates in southern Iowa after controlling for several potentially confounding factors including maternal smoking and socioeconomic variables. The association with IUGR was strongest for atrazine, but all three herbicides were intercorrelated and the independent contributions of each to IUGR risk could not be determined. We conclude that communities in southern Iowa with drinking water supplies contaminated with herbicides have elevated rates of IUGR compared to neighboring communities with different water supplies. Because of the limitations of the ecologic design of this study, including aggregate rather than individual measures of exposure and limited ability to control for confounding factors related to source of drinking water and risk of IUGR, a strong causal relationship between any specific water contaminant and risk of IUGR cannot yet be inferred. The association between the water supplied to the Rathbun communities and the increased risk of IUGR should be considered a preliminary finding that needs to be verified by more detailed epidemiologic studies.

Atrazine↗
PubMed1997

Adaptation to optokinetic rotation-induced motion sickness without experiencing nausea.

17 subjects highly susceptible to motion sickness were divided into Nausea and No-nausea groups depending upon whether the subjects experienced nausea during adaptation to nauseagenic rotation. Eight subjects in the Nausea group viewed an optokinetic rotation drum for repeated sessions of 16 min., with an interval of two days between every two sessions. During each session the subjects continuously viewed the rotating drum 16 min. even if they experienced nausea. nine subjects in the No-nausea group likewise viewed an optokinetic rotation drum for at most 16 min. but immediately stopped viewing the rotating drum whenever they experienced nausea during the session. The criteria for full adaptation were that the subject reported no feelings of stomach discomfort and nausea during a 16-min session. The mean number of sessions to reach full adaptation was 3.9 (SD = 0.6) with a range 3 to 5 sessions for the subjects in the Nausea group and 3.2 (SD = 0.8) with a range 2 to 4 for the subjects in the No-nausea group. It was concluded that subjects can adapt to a nauseagenic optokinetic rotation by repeated exposure without experiencing nausea and vomiting during adaptation.

Adaptation, Physiological↗